Transforming growth factor beta-1 (TGF-beta-1) and epinephrine have opposing effects on normal human bronchial epithelial (NHBE) cells. While TGF-beta-1 induces squamous differentiation in NHBE cells, epinephrine promotes their growth and neutralizes the effect of TGF-beta-1. To investigate mechanisms which might be involved in their antagonism, we examined steady state expression levels of proto-oncogenes c-myc, c-fos, and c-Ha-ras in response to treatment with these two agents. Expression of specific mRNA was detected by Northern blotting and normalized by the constitutive probe, glyceraldehyde-3-phosphate-dehydrogenase. Expression of c-myc was transiently inhibited by TGF-beta-1 up to 40%at 1 hr. Epinephrine induced the expression of c-myc about two- to threefold and neutralized the effect of TGF-beta-1 on c-myc mRNA level. Expression of c-fos was transiently induced by either TGF-beta-1 or epinephrine up to 1.5 or two- to threefold at 1 hr, respectively. These two agents synergistically induced c-fos up to 5 fold. The c-Ha-ras mRNA level was not altered by TGF-beta-1 or epinephrine treatments. While the initial changes in c-myc expression correlated with the proliferative activity of the cells, the steady state level of c-fos mRNA did not.